American Journal of Nephrology最新文献

{"title":"PKD1 Truncating Mutations Accelerate eGFR Decline in Autosomal Dominant Polycystic Kidney Disease Patients.","authors":"Hamad Ali, Barrak Alahmad, Sarah R Senum, Samia Warsame, Yousif Bahbahani, Mohamed Abu-Farha, Jehad Abubaker, Malak Alqaddoumi, Fahd Al-Mulla, Peter C Harris","doi":"10.1159/000536165","DOIUrl":"10.1159/000536165","url":null,"abstract":"<p><strong>Introduction: </strong>Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic disease characterized by the accumulation of fluid-filled cysts in the kidneys, leading to renal volume enlargement and progressive kidney function impairment. Disease severity, though, may vary due to allelic and genetic heterogeneity. This study aimed to determine genotype-phenotype correlations between PKD1 truncating and non-truncating mutations and kidney function decline in ADPKD patients.</p><p><strong>Methods: </strong>We established a single-center retrospective cohort study in Kuwait where we followed every patient with a confirmed PKD1-ADPKD diagnosis clinically and genetically. Renal function tests were performed annually. We fitted generalized additive mixed effects models with random intercepts for each individual to analyze repeated measures of kidney function across mutation type. We then calculated survival time to kidney failure in a cox proportional hazards model. Models were adjusted for sex, age at visit, and birth year.</p><p><strong>Results: </strong>The study included 22 truncating and 20 non-truncating (42 total) patients followed for an average of 6.6 years (range: 1-12 years). Those with PKD1 truncating mutations had a more rapid rate of eGFR decline (-4.7 mL/min/1.73 m2 per year; 95% CI: -5.0, -4.4) compared to patients with PKD1 non-truncating mutations (-3.5 mL/min/1.73 m2 per year; 95% CI: -4.0, -3.1) (p for interaction &lt;0.001). Kaplan-Meier survival analysis of time to kidney failure showed that patients with PKD1 truncating mutations had a shorter renal survival time (median 51 years) compared to those with non-truncating mutations (median 56 years) (P for log-rank = 0.008).</p><p><strong>Conclusion: </strong>In longitudinal and survival analyses, patients with PKD1 truncating mutations showed a faster decline in kidney function compared to patients PKD1 non-truncating mutations. Early identification of patients with PKD1 truncating mutations can, at best, inform early clinical interventions or, at least, help suggest aggressive monitoring.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"380-388"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139401364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Availability and Quality of Dialysis Care in Rural versus Urban US Counties.","authors":"Elizabeth Crouch, Nick Yell, Laura Herbert, Teri Browne, Peiyin Hung","doi":"10.1159/000537763","DOIUrl":"10.1159/000537763","url":null,"abstract":"<p><strong>Introduction: </strong>Rural areas face significant disparities in dialysis care compared to urban areas due to limited access to dialysis facilities, longer travel distances, and a shortage of healthcare professionals. The objective of this study was to conduct a national examination of rural-urban differences in quality of dialysis care offered across counties in the USA.</p><p><strong>Methods: </strong>Data were gathered from Medicare-certified dialysis facilities in 2020 from the Centers for Medicare and Medicaid Services website. To identify high-need counties, county-level estimated crude prevalence of diabetes in adults was obtained from the 2022 CDC PLACES data portal. Our analysis reviewed 3,141 counties in the USA. The primary outcome measured was whether the county had a dialysis facility. Among those counties that had a dialysis facility, additional outcomes were the average star rating, whether peritoneal dialysis was offered, and whether home dialysis was offered.</p><p><strong>Results: </strong>The type of services offered by dialysis facilities varied significantly, with peritoneal dialysis being the most commonly offered service (50.8%), followed by home hemodialysis (28.5%) and late-shift services (16.0%). These service availabilities are more prevalent in urban facilities than in rural facilities. The Centers for Medicare and Medicaid Services Five Star Quality ratings were quite different between urban and rural facilities, with 40.4% of rural facilities having a ranking of five, compared to 27.1% in urban.</p><p><strong>Conclusion: </strong>The majority of rural counties lack a single dialysis facility. Counties with high rates of chronic kidney disease, diabetes, and blood pressure, deemed high need, were less likely to have a highly rated dialysis facility. The findings can be used to further inform targeted efforts to increase diabetes educational programming and design appropriate interventions to those residing in rural communities and high-need counties who may need it the most.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"361-368"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139717316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Yield of Exome Sequencing in Early-Onset Hypertensive Nephropathy in Adults.","authors":"Justine Serre, Alice Doreille, Laure Raymond, Gaspard Suc, Mickaël Bobot, Marine Dancer, Cédric Rafat, Laurent Mesnard","doi":"10.1159/000538173","DOIUrl":"10.1159/000538173","url":null,"abstract":"<p><strong>Introduction: </strong>Hypertensive nephrosclerosis (HN) ranks as one of the most frequent causes of chronic kidney disease (CKD), but its very existence has repeatedly been called into question, especially in young adults. Its diagnostic framework is established chiefly on non-specific clinical criteria, and its defining histopathological set of features is in fact shared by numerous other conditions. Genetic testing based on exome sequencing (ES) has emerged as a comprehensive tool to detect Mendelian diseases in timely fashion in nephrology, with a significant number of re-established diagnoses. The aim of this study was to investigate the diagnostic yield of ES in patients with a clinical diagnosis of hypertensive nephropathy.</p><p><strong>Method: </strong>Since September 2018, ES has been readily available as part of the routine diagnostic work-up in our institution. The indication of ES includes hypertensive nephropathy of early onset (i.e., &lt;45 years old). We retrospectively collected the ES data performed in the context of hypertensive nephropathy in our institution between September 2018 and February 2021.</p><p><strong>Results: </strong>A total of 128 patients were sequenced in the context of hypertensive nephropathy with early onset. The chief indications of ES were an early onset of CKD (47%), family history of kidney disease (8%), or both (18%). We detected diagnostic variants in 19 of the 128 patients (15%), encompassing a total of 13 different monogenic disorders. The diagnostic yield of ES was lower in patients of African ancestry (diagnostic yield of 7 vs. 30% in non-African ancestry patients, p &lt; 0.001).</p><p><strong>Conclusions: </strong>The high diagnostic yield of ES (15%) in a population of patients thought to have HN casts further doubts on the validity of the existing diagnosis criteria, including histological criteria, supposed to characterize the condition. This was especially true in patients with no African ancestry, where ES positivity reached 30%.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"468-471"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140108789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Serum Activin Levels with Allograft Outcomes in Patients with Kidney Transplant: Results from the KNOW-KT.","authors":"Hui-Yun Jung, Jung-Hwa Ryu, Myung-Gyu Kim, Kyu Ha Huh, Kyo Won Lee, Hee-Yeon Jung, Kyung Pyo Kang, Han Ro, Seungyeup Han, Jaeseok Yang","doi":"10.1159/000536198","DOIUrl":"10.1159/000536198","url":null,"abstract":"<p><strong>Introduction: </strong>Serum activin A has been reported to contribute to vascular calcification and kidney fibrosis in chronic kidney disease. We aimed to investigate whether higher serum activin levels were associated with poor allograft outcomes in patients with kidney transplantation (KT).</p><p><strong>Methods: </strong>A total of 860 KT patients from KNOW-KT (Korean Cohort Study for Outcome in Patients with Kidney Transplantation) were analyzed. We measured serum activin levels pre-KT and 1 year after KT. The primary outcome was the composite of a ≥50% decline in estimated glomerular filtration rate and graft failure. Multivariable cause-specific hazard model was used to analyze association of 1-year activin levels with the primary outcome. The secondary outcome was coronary artery calcification score (CACS) at 5 years after KT.</p><p><strong>Results: </strong>During the median follow-up of 6.7 years, the primary outcome occurred in 109 (12.7%) patients. The serum activin levels at 1 year were significantly lower than those at pre-KT (488.2 ± 247.3 vs. 704.0 ± 349.6). When patients were grouped based on the median activin level at 1 year, the high-activin group had a 1.91-fold higher risk (95% CI, 1.25-2.91) for the primary outcome compared to the low-activin group. A one-standard deviation increase in activin levels as a continuous variable was associated with a 1.36-fold higher risk (95% CI, 1.16-1.60) for the primary outcome. Moreover, high activin levels were significantly associated with 1.56-fold higher CACS (95% CI, 1.12-2.18).</p><p><strong>Conclusion: </strong>Post-transplant activin levels were independently associated with allograft functions as well as coronary artery calcification in KT patients.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"245-254"},"PeriodicalIF":4.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virtual Pharmacy: An Integrated Collaborative Redesign Targeting Medication-Related Problems in Patients with Chronic Kidney Disease.","authors":"Stephanie W Ong, Abhijat Kitchlu, David Z I Cherney, Karen Leung, Christopher T M Chan","doi":"10.1159/000535094","DOIUrl":"10.1159/000535094","url":null,"abstract":"<p><strong>Introduction: </strong>Collaborative management of kidney disease relies on coordinated and effective partnerships between multiple providers. Siloed traditional health systems often result in delays, barriers to treatment access, and inefficient monitoring.</p><p><strong>Methods: </strong>We conducted a 1-year observational mixed-methods study. We included all consecutive referrals except for patients without telephone access. We assessed 4 domains of outcomes: (1) patient and caregiver experience, (2) provider experience (e.g., physicians and pharmacists), (3) clinical outcomes specific to medication-related outcomes (e.g., adherence, adverse drug events [ADEs]), and (4) value and efficiency (i.e., medication access, defined as time to treatment and resolution of medication reimbursement issues).</p><p><strong>Results: </strong>Sixty-five patients were referred to the integrated virtual pharmacy (iVRx) model. Most (72%) patients were male. Patients had a median (min, max) age of 60 (27, 85) years and were taking 8 (4, 13) medications. Compared with traditional care delivery models, medication access improved for 56% of participants. Direct home delivery of medication resulted in 91% of patients receiving prescriptions within 2 days of a nephrologist visit. During more than 2,000 pharmacist-patient encounters, 208 ADEs were identified that required clinician intervention to prevent patient harm. When these ADEs were classified by severity, 53% were mild, 45% were moderate (e.g., delaying dose titration in patients initiated on glucagon-like peptide 1 (GLP-1) agonists due to intolerable gastrointestinal side effects), and the remaining 2% of ADEs were severe, meaning clinical intervention was required to prevent a serious outcome (e.g., uncontrolled blood pressure, prevention of acute kidney injury). Nephrologists reported high satisfaction with iVRx, citing efficiency, timely response, and collaboration with pharmacists as key facilitators. Of the 65 patient participants, 98% reported being extremely satisfied.</p><p><strong>Conclusions: </strong>The iVRx is an acceptable and feasible clinical strategy. Our pilot program was associated with improved kidney care by increasing medication access for patients and avoiding potential harms associated with ADEs.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"206-213"},"PeriodicalIF":4.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71520227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient and Caregiver Perspectives on Gender Disparity in Chronic Kidney Disease: Questionnaire Survey, Based on an Interview Study.","authors":"Lenka Vanek, Dilara Gülmez, Amelie Kurnikowski, Simon Krenn, Sebastian Mussnig, Michał Lewandowski, Philipp Gauckler, Markus Pirklbauer, Sabine Horn, Maria Brunner, Emanuel Zitt, Bernhard Kirsch, Martin Windpessl, Kathrin Eller, Balasz Odler, Ida Aringer, Martin Wiesholzer, Tanja Stamm, Allison Jauré, Manfred Hecking","doi":"10.1159/000540850","DOIUrl":"10.1159/000540850","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic kidney disease (CKD) in stages 3-5 without albuminuria occurs more often in women than in men; however, most patients initiating and receiving kidney replacement therapy are men. Sex-determined biological factors and gender-related aspects both likely account for this discrepancy. Patient opinions on gender-related discrepancies in kidney care have not been investigated.</p><p><strong>Methods: </strong>Building upon the findings of semi-structured interviews previously conducted with CKD patients and their caregivers, two questionnaires were developed to investigate patient behavior and opinions relating to gender and CKD. These questionnaires containing 39 items were distributed to eight outpatient clinics in Austria. Responses were descriptively analyzed and compared between genders, as well as between age-groups and CKD stages.</p><p><strong>Results: </strong>Questionnaires from 783 patients and 98 caregivers were included in the analysis and covered health awareness and self-management of disease, the impact of gender roles and gender equality, and patient autonomy and trust in the health-care system. A total of 56.1% of men patients and 63.1% of women patients found that women were better at looking after their health compared to men (41.1%/34.3% no difference, 2.8%/2.6% men better). A total of 95.4% of men patients, 95.0% of women patients, 100% of men caregivers, and 95.5% of women caregivers stated that all patients with kidney disease were treated completely equally, irrespective of gender.</p><p><strong>Conclusion: </strong>Neither the patients nor the caregivers stated gender-determined treatment decisions in CKD care. Both men and women however agreed that women are better at maintaining their own health and excel in disease self-management.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"561-582"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperechoic Spots in the Renal Medulla as a Potential Indicator of Early Gouty Nephropathy.","authors":"Fangfang Zhang, Mengmeng Yan, Lishan Xiao, Caiyun Jiang, Changgui Li, Xiaoli Li, Meixia Du, Can Wang, Jun Li, Chunping Ning","doi":"10.1159/000541110","DOIUrl":"10.1159/000541110","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of the study was to explore the causes and clinical significance of hyperechoic renal medulla observed by ultrasonography in patients with primary gout.</p><p><strong>Methods: </strong>This study included 2,107 patients with primary gout treated in the Gout Clinic of our hospital from 2016 to 2022. The clinical data and biochemical data of these patients were collected and analyzed. According to the presence or absence of punctate hyperechogenicity in the renal medulla on ultrasound examination, the patients were divided into the hyperechoic medulla (HM) and the normal hypoechoic medulla (NM) groups, and the HM group was further divided into the partial HM (P-HM) and fulfilled HM (F-HM) subgroups according to the distribution range of hyperechogenicity.</p><p><strong>Results: </strong>Among the 2,107 patients with primary gout, 380 had hyperechoic renal medulla on renal ultrasound, including 106 patients with F-HM and 274 with P-HM. There were significant differences in the gout duration, urate arthropathy number, serum urate (SU) level, clinical tophi number, blood urea nitrogen, serum creatinine (sCr), and estimated glomerular filtration rate between the HM and NM groups or between the F-HM and P-HM subgroups (p < 0.05). Multivariate regression analysis showed that the presence of HM was positively correlated with gout duration, urate arthropathy number, gout attack frequency, SU, and sCr. The number of clinical tophi and sCr were closely related to F-HM.</p><p><strong>Conclusion: </strong>Ultrasound examination showed that a high medulla echo in patients with gout was often related to renal function damage. P-HM may be a transitory condition between NM and F-HM in patients with gout.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"657-671"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D Status and Treatment in ESKD: Links to Improved CKD-MBD Laboratory Parameters in a Real-World Setting.","authors":"Rachel M Holden, Patrick A Norman, Andrew G Day, Samuel A Silver, Kristen K Clemens, Eduard Iliescu","doi":"10.1159/000541109","DOIUrl":"10.1159/000541109","url":null,"abstract":"<p><strong>Introduction: </strong>Vitamin D insufficiency is common in patients who receive hemodialysis, yet there is no clear guidance regarding surveillance or treatment. We hypothesized that increasing 25(OH)D3 levels is associated with lower phosphate, parathyroid hormone (PTH), and alkaline phosphatase (ALP).</p><p><strong>Methods: </strong>Baseline 25(OH)D3 level was measured in all patients receiving in-center hemodialysis in June 2017. Laboratory parameters were measured every 6 (phosphate, calcium) or 12 weeks (25(OH)D3, PTH, ALP) until February 2021. In September 2018, a treatment algorithm of 50,000 IU weekly until sufficient followed by 50,000 IU monthly was suggested. Generalized linear mixed regression models including linear spline effects, a log link function, and random effects were used to examine the impact of increasing 25(OH)D3 levels on calcium, phosphate, ALP, and PTH.</p><p><strong>Results: </strong>Of 697 participants, 15% and 57% had vitamin D deficiency (25(OH)D3 <25 nmol/L) and insufficiency (between 25 and 74 nmol/L). Incorporating up to 7,272 observations, increasing 25(OH)D3 was associated with significantly decreasing PTH for 25(OH)D3 levels between 25 and 75 nmol/L regardless of vitamin D treatment. In an interaction model, the negative slope between 25(OH)D3 and PTH remained significant beyond 75 nmol/L in the absence of calcitriol. Increasing 25(OH)D3 was associated with significantly decreasing phosphate for 25(OH)D3 levels between 25 and 75 nmol/L regardless of vitamin D treatment and below 25 nmol/L in values of untreated patients. Calcium increased across the spectrum of 25(OH)D3 regardless of vitamin D treatment. Overall, 0.2% of 25(OH)D3 levels exceeded 250 nmol/L and 2.1% of calcium levels exceeded the normal range.</p><p><strong>Conclusions: </strong>Vitamin D treatment in a real-world setting was safe and associated with lower PTH levels. Whether improved biochemical markers translate to a reduction in clinical endpoints warrants further study.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"638-646"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Immunosuppressive Drug LF15-0195 Acts Also on Glomerular Lesions, by a Change in Cytoskeleton Distribution in Podocyte.","authors":"Ludmilla Le Berre, Gaëlle Tilly, Paul Pilet, Sophie Brouard, Jacques Dantal","doi":"10.1159/000539965","DOIUrl":"10.1159/000539965","url":null,"abstract":"<p><strong>Introduction: </strong>Buffalo/Mna rats spontaneously develop nephrotic syndrome (NS) which recurs after renal transplantation. The immunosuppressive drug LF15-0195 can promote regression of the initial and post-transplantation nephropathy via induction of regulatory T cells. We investigate if this drug has an additional effect on the expression and localization of podocyte specific proteins.</p><p><strong>Methods: </strong>Buffalo/Mna kidney samples were collected before and after the occurrence of proteinuria, and after the remission of proteinuria induced by LF15-0195 treatment and compared by quantitative RT-PCR, Western blot, electron, and confocal microscopy to kidney samples of age-matched healthy rats. Cytoskeleton changes were assessed in culture by stress fibers induction by TNFα.</p><p><strong>Results: </strong>We observed, by electron microscopy, a restoration of foot process architecture in the LF15-0195-treated Buff/Mna kidneys, consistent with proteinuria remission. Nephrin, podocin, CD2AP, and α-actinin-4 mRNA levels remained low during the active disease in the Buff/Mna, in comparison with healthy rats which increase, while podocalyxin and synaptopodin transcripts were elevated before the occurrence of the disease but did not differ from healthy animals after. No difference in the mRNA and protein expression between the untreated and the LF15-0195-treated proteinuric Buff/Mna were seen for these 6 proteins. No changes were observed by confocal microscopy in the protein distribution at a cellular level, but a more homogenous distribution similar to healthy rats, was observed within the glomeruli of LF15-0195-treated rats. In addition, LF15-0195 could partially restore actin cytoskeleton of endothelial cells in TNFα-induced-cell stress experiment.</p><p><strong>Conclusion: </strong>The effect of LF15-0195 treatment appears to be mediated by 2 mechanisms: an immunomodulatory effect via regulatory T cells induction, described in our previous work and which can act on immune cell involved in the disease pathogenesis, and an effect on the restoration of podocyte cytoskeleton, independent of expression levels of the proteins involved in the slit diaphragm and podocyte function, showed in this article.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"583-596"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Randomized Trial of the Impact of Ferric Citrate on Erythropoietin and Intravenous Iron Use in Patients Receiving Dialysis.","authors":"Geoffrey A Block, Mohammed Reza Mizani, Varshasb Broumand, F David Newby, Ayodele Erinle, Carolina Arias, Martha Block, Stephanie Brillhart, Amanda Leppink, Mark Danese, Mary Dittrich","doi":"10.1159/000540227","DOIUrl":"10.1159/000540227","url":null,"abstract":"<p><strong>Introduction: </strong>Ferric citrate (FC) is an FDA-approved iron-based phosphate binder for adults with dialysis-dependent chronic kidney disease. This study investigated the impact of FC as the primary phosphate-lowering therapy on utilization of erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron.</p><p><strong>Methods: </strong>In this randomized, open-label, active-controlled, multicenter study (NCT04922645), patients on dialysis and receiving ESAs were randomized to receive FC or remain on standard of care (SOC) phosphate-lowering therapy for up to 6 months. Primary endpoints were the difference in change from baseline to efficacy evaluation period (EEP) in mean monthly ESA and IV iron doses. Secondary endpoints included treatment differences in hemoglobin, phosphate, TSAT, and ferritin levels.</p><p><strong>Results: </strong>Two hundred nine patients were randomized to FC and had a day 1 dosing visit (n = 103) or SOC (n = 106). The two groups had similar baseline laboratory characteristics; however, atherosclerotic CV disease, peripheral vascular disease, and congestive heart failure were more common in the SOC group. The mean treatment difference in ESA monthly dose was -30.8 μg (FC vs. SOC; p = 0.02). An absolute though non-statistically significant change in mean monthly IV iron dose of -37.2 mg (p = 0.17) was observed with FC. Mean hemoglobin, TSAT, and ferritin all increased from baseline to the EEP with FC versus SOC. Serious adverse events occurred in 28% of patients receiving FC versus 37% in those receiving SOC.</p><p><strong>Conclusions: </strong>In patients receiving dialysis, treatment with FC as compared to remaining on SOC phosphate binders resulted in reductions in mean monthly ESA and IV iron dose.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"520-528"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}